This project is aimed at developing a molecular genetic approach for the study; classification and diagnosis of human lymphoid neoplasms including non Hodgkin's Lymphomas (NHL) and lymphoid leukemia (LL). This approach will be based on the analysis of two classes of genetic markers in lymphoid tumors. First, immunoglobulin and T-cell receptor gene rearrangements will be analysed as markers of lineage, clonality and stage of differentiation in B- and T-cell tumors respectively. Second, the expression of known cellular oncogenes will be analyzed as markers of proliferative and differentiative status of the same tumors. The results of both these analyses will correlate with immunopheno-typic, istopathologic and clinical data. In particular the research plan will involve the following specific aims: 1) Classification of stage of B-cell differentiation of lymphomas and leukemias based on Ig gene rearrangements 2) classification of stage of differentiation and functional subtype of T-cell neoplasm based on expression of T-cell receptor genes. This part of the project will involve the development of molecular probes and strategies for the detection of rearrangements of the genes coding for the alpha and gamma chain of the T-cell receptor. 3) Analysis of pattern of oncogene expression in different tumor subtypes and correlation with immunogenotypically determined stages of differentiation. 4) Application of the assays for identification of B- and T-cell clones to a number of important clinical questions including: a) identification of minimal residual disease during tumor remission b) identification of and comparative analysis of clonal populations during different stages, i.e. onset and relapses of a given malignancy.